Summary

Objective. To assess the safety and efficacy of a fixed dose of
recombinant activated factor VII (rFVIIa; NovoSeven™) in the home
setting for mild to moderately severe joint, muscle, and mucocutaneous
bleeding episodes in patients with haemophilia A or B with inhibitors.
Design. Multicentre, open-label, single arm, phase III study of one year
duration. Methods. Patients or their caregivers administered up to three
doses of rFVIIa (90 mg/kg i.v.) at 3 h intervals within 8 h of the onset of
a mild to moderate bleeding episode. Once the subject considered that
rFVIIa had been “effective” with regard to haemostasis (after 1-3 injec-tions),
one further (maintenance) dose of rFVIIa was administered.
Results. Of 60 patients enrolled, 56 experienced at least one bleed, and
46 completed the one year study. 614 of 877 bleeds (70%) were
evaluable according to protocol definitions. Haemostasis was rated as
“effective” in 92% (566/614) of evaluable bleeds after a mean of 2.2
injections. For successfully treated episodes, the time from onset of
bleeding until administration of the first injection was 1.1 ± 2.0 h
(mean ± SD). Twenty-four hours after initial successful response,
haemostasis was reported as having been maintained in 95% of cases.
Efficacy was comparable for muscle, joint and target joint, and muco-cutaneous
bleeding episodes. In an intent-to-treat analysis of all 877
bleeding events, efficacy outcomes were equivalent to the evaluable
bleeds, with an effective response in 88% of treated episodes. Treat-ment-
related adverse events occurred in 32 (3% of all) bleeding epi-sodes
and consisted of re-bleeds/new bleeds in more than 50% (18/32)
of these events. A single episode of superficial thrombophlebitis was
the only thrombotic complication encountered, and there were no
patient withdrawals due to adverse events. Development of FVII(a)
antibodies could not be detected, and hypersensitivity reactions to
rFVIIa were not reported. Conclusion. rFVIIa is effective and well
tolerated when used in the home setting to treat mild to moderate
bleeding episodes in patients with haemophilia A or B with inhibitors.